Buprenorphine Formulations Research Articles (Page 1)

Long-Acting injectable buprenorphine PLGA microparticle formulation.

Overdose risk profiles in pregnancy: Latent class analysis of pregnant individuals with opioid use disorder.

Long acting (or extended release) injectable buprenorphine formulations for the treatment of opioid dependence have been introduced in a number of countries in recent years. One such product, Buvidal, available as Weekly or Monthly subcutaneous injections, has been increasingly used in many European countries and Australia for several years, and has recently been registered under the brand name Brixadi in the United States. This review provides an overview of opioid dependence, examines the rationale for the development of Buvidal, its pharmacological properties, evidence of efficacy and safety, and key principles of clinical care in the treatment of opioid dependence. Particular attention is given to issues of pain management, pregnancy, and treatment in custodial settings. This long-acting injectable buprenorphine product is an important addition to the available options for the treatment of opioid dependence, providing a safe and effective alternative to treatment with medications requiring daily dosing.

Buprenorphine is an opioid used for pain management in veterinary medicine but which requires frequent dosing to maintain therapeutic levels. Sustained-release buprenorphine (BSR) formulations can overcome this limitation, but genera- or species-specific studies that determine the time profiles of buprenorphine after dosing are sparse for NHPs. The objective of this study was to determine the plasma buprenorphine concentrations for 72 hours after a single subcutaneous administration of 0.2 mg/kg BSR or Ethiqa XR (EXR), an FDA-indexed, extended-release buprenorphine formulation, in owl monkeys. Blood samples were taken before and at 1, 4, 8, 24, 48, and 72 hours after administering either formulation to determine plasma buprenorphine concentrations. Clinical observations were also performed. A single 0.2 mg/kg dose of BSR and EXR raised plasma buprenorphine concentrations above the hypothesized therapeutic threshold for NHPs of 0.1 ng/mL within 1 hour of administration and maintained these levels for at least 72 hours. However, this dose did not sustain buprenorphine concentrations above the human efficacy threshold of 0.5 ng/mL for 72 hours. A subsequent study evaluated a single dose of 0.3 mg/kg EXR to determine whether this dose sustained plasma buprenorphine levels >0.5 ng/mL for 72 hours. Most owl monkeys reached this threshold and maintained plasma buprenorphine concentrations >0.5 ng/mL with this dose, albeit with increased side effects, including sedation and ptyalism. Injection site reactions were not observed in any animals during any study. In sum, this work indicates that a single subcutaneous dose of 0.2 mg/kg BSR or EXR can maintain buprenorphine above the hypothesized therapeutic threshold for NHPs of 0.1 ng/mL for 72 hours, but the EXR dose must be increased to reach the human efficacy threshold for 72 hours in owl monkeys.

Injectable buprenorphine during transition out of prison: A pilot partially randomized preference trial protocol.

Buprenorphine is a commonly used analgesic in laboratory rodents for procedures of moderate to severe pain. We evaluated the pharmacokinetic properties of an immediate-release formulation of buprenorphine (Bup-IR) and an extended-release formulation (Bup-ER) in both sexes of 4 different strains of mice (C57BL/6, CD-1, BALB/c, and CB17 SCID) commonly used for dermatology and oncology research at our institution. Skin at the injection site was evaluated for 7 days postinoculation and scored for reactions and then collected for histopathologic analyses. Body weights were evaluated at 1 and 4 days postinoculation. We hypothesized that the administration of Bup-ER would provide a longer duration of blood drug concentration (>1 ng/mL; minimum analgesia threshold) compared with single-dose Bup-IR. We analyzed the standard dose for Bup-IR (0.3 mg/kg) and for Bup-ER (1 mg/kg), along with saline vehicle with blood collected at 1, 4, 24, 48, 72, and 96 hours following administration of Bup-ER and 0.25, 0.5, 1, 2, 3, 6, 9, 12, and 24 hours following administration of Bup-IR using MS. Bup-ER and Bup-IR levels were consistent among sexes of a given strain but varied between strains. Skin reactions, body weight loss, and histopathologic changes were greater in the Bup-ER-treated mice with some sex and strain differences. Due to changes found on histopathology of the skin sections taken from the injection site for Bup-ER-inoculated mice, a separate study to determine cytokine release following Bup-ER injection was performed and revealed only minor changes in a few cytokines. In conclusion, Bup-ER provided longer duration analgesia (>1 ng/mL) compared with Bup-IR. Based on differences found in the strains of mice evaluated, we recommend performing pharmacokinetic analyses for a given strain to determine the best dosing frequency and dose of buprenorphine (IR or ER) for procedures that require analgesia.

Laboratory rats (Rattus norvegicus) are common animal models used in biomedical, psychological, and toxicological research. Their long-established research use has driven the progressive refinement of experimental techniques so that associated pain/distress may be ameliorated. One of these refinements is the use of opioids to provide analgesia. Buprenorphine, a partial mu-opioid agonist with high affinity for mu receptors, is commonly used for rodents, as the longer duration of action compared with morphine reduces the need for direct handling during administration of supplemental doses. While conventional buprenorphine (CB) requires dosing two to four times per day to provide sufficient pain control in many mammalian species, a novel, highly concentrated formulation of buprenorphine (HCB; Simbadol) is the first FDA-approved, veterinary-specific opioid labeled for every 24-hour dosing in cats (Felis catus). We hypothesized that, at the labeled feline dose of 0.24 mg/kg SC, HCB would achieve buprenorphine serum concentrations ≥1 ng/mL in older adult female Sprague-Dawley rats for at least 12 to 24 hours. Mean peak serum concentrations of 13.79 ± 6.76 ng/mL occurred 0.5 hour after administration. Twelve hours postadministration, the mean serum concentration was 2.12 ± 0.59 ng/mL with all treated rats maintaining individual serum concentrations well above 1 ng/mL. Twenty-four hours postadministration, the mean serum concentration was 1.02 ± 0.33 ng/mL with 4 of 6 rats maintaining individual serum concentrations of greater than or equal to 0.99 ng/mL. With the exception of a minor, focal injection site reaction in one animal, none of the other known side effects of opioid administration in rats were observed. These results support that administration of HCB at 0.24 mg/kg SC to older adult female SD rats produces serum buprenorphine concentrations consistent with analgesia for at least 12 hours and for up to 24 hours in some rats.

Opioids are widely used in the management of acute postoperative pain after thoracic surgery. Buprenorphine (BUP), though discovered as an analgesic, with robust evidence supporting its efficacy for this purpose, and possessing important safety advantages compared with commonly used full agonist opioids, is currently rarely used for acute pain management. To assess feasibility of implementing buccal BUP as part of a multimodal analgesia strategy, and to conduct an exploratory comparison of pain outcomes between patients receiving buccal BUP in addition to standard postoperative pain management, and patients receiving standard postoperative pain management alone. Retrospective cohort. Veterans Health Administration. In this single-center, retrospective cohort study of patients undergoing minimally invasive lung surgery, we assessed feasibility of buccal BUP administration for perioperative pain management, and conducted an exploratory analysis of pain outcomes in 29 patients, a subset of which received perioperative buccal BUP. Buccal BUP is feasible, safe, and is associated with improved pain outcomes after thoracic surgery. This retrospective review within a relatively homogenous population lacks a randomization process and size to address bias and confounding. Further study is needed to confirm any identified associations. We did not assess long-term outcomes, such as function and persistent opioid use. We are not aware of prior study of the buccal formulation of BUP for acute pain management. In this retrospective cohort study of largely opioid-naive patients undergoing thoracic surgery, buccal BUP was feasible, safe, and was associated with reduced pain postoperatively.

Rabbits are commonly used as surgical models, thus requiring analgesics for painful procedures and optimal animal welfare. Buprenorphine, a partial µ opioid, is commercially available in various concentrations and sustained-release formulations and has historically been used as an analgesic in rabbits. A topical long-acting buprenorphine formulation (Zorbium, Bup-TP) has been approved for analgesic use in cats but has not yet been evaluated in rabbits. The present study evaluated the plasma concentrations and pharmacokinetic parameters of Bup-TP in New Zealand white rabbits (Oryctolagus cuniculus). Healthy adult male (n = 4) and female (n = 4) New Zealand white rabbits were used in a randomized crossover design and received a single high (7 mg/kg) and low (3 mg/kg) dose of Bup-TP. In this study, Bup-TP achieved a plasma blood concentration >0.25 ng/mL starting at 0.5 hours after dosing that was maintained up to 72 hours after dosing in adult New Zealand white rabbits. Compared with baseline, fecal and urinary output were reduced for an average of 3.5 days after dosing; food consumption was reduced for an average of 10 days after dosing. All resolved with time and supportive care. No lesions were grossly visible on any rabbit at site of application. Bup-TP may be an effective, long-lasting, and noninvasive method of providing analgesia in rabbits. Future study is recommended to optimize dosing and procedural analgesic efficacy.

From Addiction to Acute Pain Relief: A Narrative Review on Buprenorphine's Expanding Role in Emergency Department Pain Management.

Opioids remain in common use for postoperative pain management after orthopedic surgery. Buprenorphine (BUP) is a partial agonist opioid best known as a lifesaving medication for opioid use disorder. Although extensively studied for acute pain management with at least the efficacy as full agonist opioids (FAO) and a superior safety profile, it is rarely used for this purpose in contemporary practice. To assess feasibility of inpatient administration of buccal BUP, in addition to usual analgesic care, and conduct an exploratory analysis of pain outcomes in an orthopedic surgery population, including a subset who received twice-daily buccal BUP. Retrospective cohort. Veterans Health Administration. A cohort of patients were treated with buccal BUP perioperatively at the discretion of the anesthesiologist. We subsequently undertook a retrospective chart review of 35 recent orthopedic cases at our institution over several months, including the subset who received buccal BUP, aiming to assess the feasibility of its use and make a preliminary assessment of pain outcomes. Our review found that perioperative buccal BUP was feasible within a population of largely opioid-naïve patients undergoing major orthopedic surgery. Pain outcomes were similar between the groups receiving BUP, in addition to usual care, and those not receiving BUP in addition to usual care. This is a retrospective review and lacks a randomization process and size to address bias and confounding. The largely homogenous patient population further limits generalizability. As such, no conclusions, generalizable or otherwise, should be made about any of the observed results. To our knowledge, the buccal formulation of BUP, which received US Food and Drug Administration approval for chronic pain management in 2015, has not been studied for acute pain management. In a population undergoing total joint arthroplasty, buccal BUP was readily accepted by patients and nursing staff, resulted in pain and opioid consumption outcomes similar to the usual care, was compatible with FAO, and resulted in no safety concerns. Given its expected safety advantages over FAO, BUP deserves further consideration and study as an opioid analgesic within a multimodal analgesic regimen.

Clinical Perspectives: Navigating Buprenorphine Formulations for Pain Treatment and Opioid Use Disorder - A Case-Based Approach.

There are racial and ethnic disparities in opioid use disorder (OUD) treatment engagement during and after emergency department (ED) encounters. To identify patterns of barriers and facilitators to treatment engagement after an ED visit among Black, Hispanic, and White individuals with OUD. This qualitative study was conducted from June 2023 to May 2024 using in-depth semistructured individual telephone interviews. Participants with OUD were previously enrolled in a multisite study comparing 2 formulations of buprenorphine in ED patients with untreated OUD on treatment engagement. A diagnosis of moderate-to-severe OUD and a visit to an ED. The primary outcome was identification of key themes at both the behavioral and health system levels associated with treatment engagement, identified through thematic analysis of interview data. A total of 57 individuals (20 female [35.1%]; mean [SD] age, 41.7 [12.8] years; 20 Black [35.1%]; 17 Hispanic [29.8%]; 20 White [35.1%]) participated in the study. Although racial and ethnic group-specific factors existed, common barriers to treatment engagement included stigma, structural factors (eg, transportation and insurance), uncertainty navigating the health system, and mental health issues. Black participants specifically described how previous trauma and daily stress contributed to a lack of treatment engagement. Black and Hispanic participants expressed experiences of racism and mistrust within the health system. Hispanic and White participants expressed concerns about the adverse effects and taste of sublingual buprenorphine. Common facilitators included positive attitudes toward treatment and patient experiences with ED staff and stable health care access. Hispanic participants described family support as a crucial factor toward treatment engagement. Black participants expressed the importance of connecting with individuals who were abstinent. In this qualitative study of 57 individuals with OUD previously treated in the ED, common themes emerged across racial and ethnic groups. However, Black, Hispanic, and White individuals with OUD encountered distinct barriers and facilitators to treatment engagement after an ED visit, such as the importance of family support among Hispanic individuals as a facilitator and experiences of racism within the health system among both Black and Hispanic individuals as a barrier. Future ED-based interventions should address disparities by reducing barriers and enhancing facilitators to improve equitable treatment access.

Buprenorphine treatment for opioid-use disorder (OUD) is commonly available in both sublingual tablets/films and extended-release subcutaneous injections; however, little is known about differences in patient retention between these two buprenorphine formulations. This study measured retention differences between patients who transitioned from sublingual to subcutaneous injectable buprenorphine and those who remained on sublingual buprenorphine throughout treatment, within a multi-location outpatient addiction treatment practice. This study was an observational propensity score-matched cohort study conducted at a multi-location outpatient addiction practice in Maryland, USA. Participants included 3609 patients receiving buprenorphine treatment for OUD between June 2019 and February 2024. Patient demographics, health history and urine toxicology results. The primary outcome was time-to-dropout in days. Kaplan-Meier and Cox Proportional Hazard models with propensity score matching were used to compare treatment retention between injectable and sublingual buprenorphine receipt. Overall, 538 patients at the time of their first extended-release buprenorphine injection (INJ) were matched with 538 patients only receiving sublingual buprenorphine (SUB-only). In the unmatched sample, INJ patients were more likely than SUB-only patients to be female (INJ 47.2% vs SUB-only 38.7%, P < 0.001) and more likely to have at least an associate's degree (41.4% vs 33.9%, P < 0.001). After matching, patients who transitioned to INJ buprenorphine had lower retention in treatment compared with patients who remained on SUB buprenorphine. Median (95% confidence interval) time-to-dropout was 269 days (218-313) for INJ patients compared with 389 days (313-592) for SUB-only patients (stratified log-rank test = 13.6, P < 0.001). Among patients receiving medication treatment for opioid use disorder in an outpatient setting, those who transitioned from sublingual to subcutaneous injectable buprenorphine were at an increased risk for dropout compared with matched patients who only received sublingual buprenorphine.

Clinical pharmacist practitioners prescribing of buprenorphine for opioid use disorder.

Aims: To identify any patients on OST who have not been offered or received naloxone.To improve documentation of naloxone provision.To explore reasons why clients have declined naloxone.The standard audited against was that 100% of clients prescribed OST should be offered naloxone. This is advised in the Department of Health publication “Drug misuse and dependence, UK guidelines on clinical management”, which advises services should be “offering all opiate users in the community access to a take-home supply of naloxone with instructions on its use”.CGL is a charity which provides medical and psychosocial support for people who are affected by alcohol and drugs. As of January 2025, they prescribe Opiate Substitute Treatment (OST), typically a formulation of methadone or buprenorphine, to 748 clients in East Sussex. Naloxone is an opioid antagonist which can reverse the effects of opiate overdose, and is offered to service users to reduce mortality from overdose.Methods: It was recorded for each of the 748 clients whether they had been offered naloxone and training, and whether they had accepted. The data were collected from the CGL County-wide Opiate report in January 2025, and cross-referenced with a manual review of notes on Criis, the electronic clinical notes platform used by CGL.Results: Of the 748 clients prescribed OST, 65 total clients did not have naloxone (8.7%), while 60 had expired naloxone. 54 clients did not have naloxone documented in the opiate report, but on a manual review of notes it was confirmed to have been given, but the dispensing form had not been completed on Criis. Of the 65 clients without naloxone, 100% had been offered naloxone and had declined.Conclusion: The manual review of notes showed that naloxone uptake was better than the opiate report suggested, due to a lack of coding. Most commonly, this was a result of clients already having naloxone from another service or from earlier course of treatment. A potential barrier is the data entry required – if a client was dispensed from another location, it must also be confirmed by the keyworker and manually entered into a form on Criis.The keyworkers of those clients with expired naloxone were informed, to arrange suitable follow-up.The most common reason for declining naloxone was that the client was no longer injecting, and had no contacts who used opiates (57%). Also mentioned was the stigma of carrying naloxone, and the fear that others would assume they had relapsed.

To evaluate the duration of action and antinociceptive and sedative effects of buprenorphine hydrochloride following SC administration to orange-winged Amazon parrots (Amazona amazonica). 10 adult, healthy Amazon parrots were included. High-concentration buprenorphine formulation (1.8 mg/mL and 0.1, 1, and 2 mg/kg) and saline solution (0.9% NaCl; 0.55 mL/kg) were administered SC to the parrots in a within-subjects, complete, masked crossover study design. Foot withdrawal thermal threshold was determined prior to administration of treatment and 0.5, 1.5, 3, and 6 hours postinjection. Agitation-sedation scores were determined 1 to 2 minutes prior to each thermal challenge. Buprenorphine at 2 mg/kg significantly increased the thermal foot withdrawal threshold, whereas lower doses evaluated did not have a significant effect. Although no significant interaction effect of treatment*time was observed, the graphical data suggest that the effect could increase over time and still be present at the 6-hour time point. No significant effect of buprenorphine on agitation-sedation score or nausea-like behavior was observed. SC administration of buprenorphine at 2 mg/kg has a mild thermal antinociceptive effect in orange-winged Amazon parrots, which graphically appears to have a slow onset and last for the duration of the testing times. In addition, buprenorphine did not cause agitation or sedation, nausea-like behavior, or vomiting. Further studies are needed to fully evaluate the effects of buprenorphine in psittacines. Buprenorphine hydrochloride could be considered for pain management in the orange-winged Amazon parrot and does not cause significant adverse effects following single SC administration.

Rats regularly undergo surgical procedures that may result in pain. Alleviation of unnecessary pain is an ethical and regulatory responsibility. Buprenorphine is an opioid analgesic commonly used in rats and requires dosing every 6 to 8 h to be effective. Frequent administration is time consuming and may increase stress, post-surgical pain, and dehiscence in rats, making the use of long-acting formulations an attractive alternative. A transdermal buprenorphine solution (TBS), FDA approved for use in felines, is commercially available and effective for up to 96 h. We hypothesize that a single dose of TBS in rats will result in clinically relevant plasma buprenorphine concentrations (greater than 1 ng/mL) for up to 96 h. To test this, 39 rats were randomly assigned to the following treatment groups: low dose (LD; 5 mg/kg; n = 6 females, 6 males), high dose (HD; 10 mg/kg; n = 6 females, 6 males), and vehicle control (CON; n = 7 females, 8 males). TBS or anhydrous ethanol (CON) were topically applied. Blood was collected at 4, 24, 72, 96, and 168 h postadministration, and buprenorphine concentrations were determined via HPLC-MS. To quantitatively assess adverse effects, daily fecal output, food intake, and body weight were measured, and observations of hematuria and skin lesions were documented. Plasma buprenorphine concentrations exceeded 1 ng/mL in all TBS rats at 4, 24, 48, and 72 h. No rats experienced serious adverse effects or developed gross lesions at the application site. The HD group had decreased fecal output compared with CON. Both TBS groups had reduced weight gain compared with CON. These results suggest that TBS dosed at 5 to 10 mg/kg could provide analgesia for up to 3 d in rats, and administering a lower dose mitigates some adverse effects.

Extended-release buprenorphine formulations are commonly used to control postoperative pain in rodents with minimal handling-related stress. An FDA-indexed formulation is now available that has been demonstrated safe and effective with ketamine-xylazine and isoflurane anesthesia; however, safe use in combination with tribromoethanol, a nonpharmaceutical-grade anesthetic sometimes favored for short, high-volume procedures, has not been reported. Effects on pregnancy and offspring have also not been examined. In this study we compared the safety and efficacy of the FDA-indexed formulation at the labeled dose (3.25 mg/kg) to the compounded extended-release buprenorphine formulation used by the centralized Transgenic Core at our institution at the manufacturer-recommended dosage (1 mg/kg) in CD-1 mice under tribromoethanol anesthesia. A pilot (n = 5 females per drug) was initially conducted with anesthetic and analgesic in the absence of surgical manipulation, after which the formulations were compared in embryo transfer and vasectomy surgeries (n = 10 males or females per drug). Relative efficacy was assessed at 6, 24, 48, and 72 h after surgery using a cageside ethogram, frequency of rearing behavior compared with baseline, and weight change. No differences were seen between analgesic treatment groups. Safety was evaluated by intraoperative respiratory rate, recovery time, incidence of analgesic injection site lesions, and gross necropsy. Ulceration was only observed at the injection site of mice receiving compounded drug; no other differences between treatments were observed. Effects on pregnancy were evaluated by comparing pregnancy success, litter size, and pup weight at weaning between treatment groups in the initial experiment and embryo transfers subsequently performed by the Transgenic Core (n = 19 sets). No significant differences were identified. These results indicate that both formulations can be safely used in vasectomy and embryo transfer surgeries under tribromoethanol anesthesia; however, the FDA-indexed product may improve welfare by decreasing injection site ulceration compared with the compounded formulation.

The FDA has approved changes to the labeling of Sublocade (Indivior), an extended-release formulation of the partial opioid agonist buprenorphine, to permit faster initiation and use of alternative injection sites. Sublocade is indicated for once-monthly subcutaneous treatment of moderate to severe opioid use disorder.